Hlj2 effectively ameliorates colitis-associated cancer via inhibition of nf-κb and epithelial– mesenchymal transition

Abstract

Introduction: Colitis-associated cancer (CAC) accounts for approximately 15% of IBD patient mortalities. However, currently available anti-CAC drugs possess many disadvan-tages including safety, specificity and side effects. Therefore, the development of novel anti-CAC compounds is imperative. HLJ2 was a monomeric compound synthesized by our institute and reported to have an effect on ulcer colitis. Methods: In vivo the AOM/DSS-induced CAC model was used to evaluate the effects of HLJ2 on ameliorating CAC symptoms, immunohistochemical analysis was used to analyze the pathological damage to colons and epithelial–mesenchymal transition was for changes of cytokines. In vitro, flow cytometric analysis, immunofluorescence and Western blot were used to detect the inhibition effect of HLJ2 on nuclear factor-κB and epithelial–mesenchymal transition in TGF-β1-stimulated SW480 cells. Results: In the AOM/DSS animal model, HLJ2 was demonstrated to inhibit the secretion of inflammatory cytokines and nuclear factor-κB, levels of tumorigenesis-related proteins including snail, and finally inhibited a key step in metastasis, epithelial–mesenchymal transition. In vitro, HLJ2 was also shown to inhibit nuclear factor-κB and epithelial– mesenchymal transition in TGF-β1-stimulated SW480 cells in accordance with in vivo results. Meanwhile, the nuclear factor-κB inhibitor could interrupt the effect of HLJ2 on epithelial–mesenchymal transition. Discussion: HLJ2 may ameliorate CAC through inhibiting nuclear factor-κB and then downstream epithelial–mesenchymal transition. The combination of the obvious improve-ment in effects on CAC without obvious side effects suggests that HLJ2 could be developed as a potential CAC therapeutic candidate.